Anthraquinone compounds from Morinda officinalis inhibit osteoclastic bone resorption in vitro

The root of Morinda officinalis has been claimed to have a protective effect against bone loss in sciatic neurectomized and ovariectomized osteoporotic rats, and this protective effect is supposed to be attributed to anthraquinone compounds in the plant. In the present study, we investigated the effects of three anthraquinones isolated from M. officinalis, including 1, 3, 8-trihydroxy-2-methoxy-anthraquinone (1), 2-hydroxy-1-methoxy-anthraquinone (2) and rubiadin (3) on bone resorption activity in vitro and the mechanism on osteoclasts derived from rat bone marrow cells. Compound 1, 2 and 3 decreased the formation of bone resorption pits, the number of multinucleated osteoclasts, and the activity of tartrate resistant acid phosphates (TRAP) and cathepsin K in the coculture system of osteoblasts and bone marrow cells in the presence of 1, 25-dihydroxyvitamine D3 and dexamethasone. They also enhanced the apoptosis of osteoclasts induced from bone marrow cells with M-CSF and RANKL. In addition, Compound 1, 2 and 3 improved the ratio of mRNA and protein expression of OPG and RANKL in osteoblasts, interfered with the JNK and NF-κB signal pathway, and reduced the expression of calcitonin receptor (CTR) and carbonic anhydrase/II (CA II) in osteoclasts induced from bone marrow cells with M-CSF and RANKL. These findings indicate that the anthraquinone compounds from M. officinalis are potential inhibitors of bone resorption, and may also serve as evidence to explain the mechanism of the inhibitory effects of some other reported anthraquinones on bone loss.

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► We examine the effects of anthraquinones on bone resorption of osteoclasts.
► Anthraquinones regulate OPG and RANKL of osteoblast to inhibit osteoclast formation.
► Anthraquinones induce osteoclastic apoptosis through disturbing JNK and NF-κB.
► Anthraquinones reduce bone resorption by modulating CA II and CTR of osteoclasts.